A renewal project is proposed to continue to develop marine microorganisms as a new source for antitumor-antibiotics. The project continues as a collaboration between marine natural products chemists and microbiologists at the Scripps Institution of Oceanography (UC-San Diego) and the Oncology Drug Discovery Group at the Bristol-Myers Squibb (BMS), Pharmaceutical Research Institute, in Princeton, NJ. The new project period would emphasize the following collaborative activities aimed at the discovery and development of new agents for the treatment of cancer: - The isolation, cultivation and screening of approximately 1,000 diverse marine microorganisms per year, focusing on marine actinomycetes, Gram- positive unicellular bacteria, gliding bacteria (both cytophaga-like forms and myxobacteria), and, in collaboration with an expert mycologist, to study fungi forming specific associations with marine plants and crustaceans. - The isolation of new bioactive agents, mainly antitumor agents, from cultured marine microorganisms, using a variety of targeted drug discovery screens, including inhibition of topoisomerase I, inhibition of microtubule polymerization and depolymerization, an in vitro cell differentiation assay, an epidermal growth factor (EGF) agonist and antagonist assay and in vitro cytotoxicity testing using drug resistant cell lines. These primary screens will be followed by evaluation in several in vivo murine models, developed in response to the specific biochemistries of these targeted screens. - To continue to develop new understanding of the locations and nutrient adaptations of marine microorganisms as a prerequisite to comprehensive evaluation of chemically-rich taxa found in marine environments. - To continue to create a large, cryopreserved marine microorganism collection, composed of diverse taxonomic groups, to serve as a basis for expanded investigation of this developing resource.